The present invention relates to the field of thermal therapy for treatment for various medical conditions, for example, tumors, and is concerned with ultrasound therapy, more particularly the devices and methods of use of such devices.
Thermal therapy is a technique for the treatment of tumors in which heat is used to destroy cancerous tissue. It is a potential candidate for the treatment of solid, localized tumors in tissue. xe2x80x9cHyperthermiaxe2x80x9d refers to thermal therapies in which the target temperatures achieved in tissue are between 42 and 46xc2x0 C. In this temperature region, the relationship between cell death, temperature and time is described by a thermal dose equation, and exposure times are typically between 30 and 60 minutes at 43-45xc2x0 C. (Dewey, 1994). Thermal coagulation refers to thermal therapies in which target temperatures achieved in tissue are between 55 and 90xc2x0 C. The application of temperatures in excess of 55xc2x0 C. results in rapid destruction of tissue primarily through thermal coagulation. This higher temperature regime delivers sufficient energy to denature proteins and produces complete cell death in the treated region within a short time (seconds) (Thomsen, 1991).
The use of thermal coagulation for tissue destruction is predicated on effective guidance and monitoring of heat delivery. Real-time medical imaging plays an integral role, providing important information about anatomy, temperature, and tissue viability during and after the delivery of heat. This information can be used to target heat delivery to specific locations, monitor the amount of heat delivered, and assess the biological damage incurred, thereby eliminating the need to expose the treatment site to visual assessment. Monitoring the spatial delivery of heat with magnetic resonance imaging (MR) can avoid damage to critical structures and other normal tissue.
In interstitial thermal therapy, heat is produced by devices inserted directly into a target site within an organ. Potentially less invasive than conventional surgery, this approach can make possible the treatment of tumors in otherwise inaccessible locations. Several technologies have been employed for interstitial heating, including lasers, radio-frequency waves, and microwaves. These devices have been shown to be capable of generating temperature elevations sufficient for thermal coagulation of tissue. Some characteristics of these devices, however, limit their ability to treat large volumes or regions close to important anatomical structures. High temperatures ( greater than 90xc2x0 C.) close to the device surface often leads to undesirable physical effects of charring or vaporization in tissue. Inadequate heating can occur at the target boundary due to rapid decreases in deposited power with increasing distance from the device. A common characteristic among existing interstitial devices is the shape of the spatial heating pattern, usually spherical or ellipsoidal. This property makes the treatment of asymmetrically shaped volumes of tissue difficult. The goal with interstitial thermal devices is to deliver a heating pattern which is as uniform as possible to the entire target volume of tissue, while avoiding excessive or inadequate heating.
The ability to generate rapid, localized temperature increases in tissue has led to the development of focused ultrasound as a method to treat tumors. Magnetic resonance (MR) imaging is well suited for use in conjunction with high intensity ultrasound as a means of treatment guidance and monitoring. MR-derived information can indicate beam position, tissue temperature, and can distinguish regions of thermal coagulation (McDannold et al., 1998; de Poorter et al., 1996; Chung et al., 1996). The feasibility of MRI-guided therapy with high intensity ultrasound has been demonstrated (Hynynen et al., 1996).
High intensity ultrasound treatment requires the coagulation of all the tissue within the tumor volume (Malcolm and ter Haar, 1996). In the case of a focused beam from an external transducer, multiple small lesions are placed throughout the target volume. For complete tumor coagulation, lesions must be closely spaced or overlapped, but gaps in coverage and unpredictable lesion formation can occur due to changes in the acoustic properties of heated tissue (Chen et al., 1997; Damianou et al., 1997).
A confounding factor, in the case of externally focused ultrasound is the heating of intervening tissue in the nearfield of the acoustic beam (Damianou and Hynynen, 1993). In the extreme case, this can result in burning of the skin (Rivens et al., 1996). To overcome this problem, sonications are separated by sufficient time for intervening areas to cool down, usually 1-2 minutes (Fan and Hynynen, 1996). This approach can reduce damage to intervening layers of tissue but treatment times become unacceptably long (1-2 hours). Transducer systems have, thus, been designed to coagulate larger volumes per sonication in an effort to reduce treatment times (Fjield et al., 1997; Ebbini and Cain, 1988; Lizzi et al., 1996, McGough et al., 1994).
A different approach is to use interstitial ultrasound heating applicators designed for insertion into tissue under image guidance, which deposit energy directly within a targeted region. The delivery of ultrasound is localized to the tumor, and the problem of heating intervening tissue layers is avoided. Interstitial transducers have been developed for a variety of applications including cardiac ablation (Zimmer et al., 1995), prostate cancer (Deardorff et al., 1998), and gastrointestinal coagulation (Lafon et al., 1998).
Scanning an acoustic beam permits the energy concentrated in the acoustic field to be distributed over a volume. This can result in more uniform heating of a larger region of tissue. The effects of scanning an acoustic beam for hyperthermia (Hynynen et al., 1986; Moros et al., 1988), and more recently for high intensity thermal coagulation (Chen et al., 1997) have been studied. At acoustic intensities sufficient for tissue coagulation, scanning generated continuous regions of thermal damage in excised liver specimens (Chen et al., 1997). This scanning technique is unsuitable for external ultrasound therapy due to excess nearfield heating, but is potentially well advantageous for interstitial ultrasound heating.
The main limitation with current interstitial devices is the output power of the transducers, due to their small size. High power is required to generate thermal coagulation in tissue within a reasonable time with a scanned acoustic beam. Effects of local blood flow could result in incomplete thermal coagulation if insufficient power is generated. With adequate power, however, the potential exists for the coagulation of large regions of tissue with interstitial ultrasound for treatment of tumors.
The theoretical heating patterns of single element and linear array transducers has been investigated in a previous study by Chopra et al. (2000). These calculations indicated the differences in the heating patterns from the two transducer designs, and highlighted the importance of achieving a high output acoustic power. However, there is a continuing need for a heating device which is able to deliver a uniform heating pattern to a target volume of tissue.
The present invention overcomes limitations of the prior art by providing an ultrasound heating applicator for thermal therapy of tissue. Preferably, an applicator according to the invention is compatible with imaging, more preferably MR imaging. Such an applicator is also preferably compatible with image-guided interstitial therapy, preferably of benign or malignant tissues. In its broad aspect the interstitial ultrasound applicator of the present invention is comprised of a transducer, preferably planar, with multiple acoustic matching layers enabling operation at a range of frequencies for optimal xe2x80x9ccontrolxe2x80x9d of the depth of thermal coagulation.
In an embodiment of the present invention, an applicator has the capability for varying the frequency of each individual element thereby enabling the tissue temperature to be adjusted both radially and along the length of the applicator or catheter. This provides critical adjustability for accommodating irregular tumor geometry, heterogeneities of the tissue thermal properties, and dynamic changes in perfusion. In addition, the heat deposition pattern is not significantly dependent on the length of insertion or placement of the device with regard to the target or other devices in the implant.
Accordingly, the present invention provides a device for thermal coagulation of tissue comprising:
(a) a multifrequency ultrasound transducer for providing acoustic energy at multiple discrete frequencies, the transducer having at least one matching layer comprising a high acoustic impedance material having an acoustic impedance comparable to the acoustic impedance of the transducer for generating acoustic energy at discrete frequencies with high efficiency of acoustic energy transmission;
(b) a housing for the transducer;
(c) means for delivery of variable frequency and power to the transducer; and,
(d) an acoustic window. Preferably the device further comprises a motor control system and means to control frequency and power of ultrasound simultaneously and independently, wherein the motor control system provides rotational control of the device to isolate heating to parts of tissue, means to control frequency and power allow for adjustment of the depth of thermal coagulation. Preferably the transducer of a device of the invention is a multiple element transducer with at least one matching layer.
In another embodiment the transducer is a multi-element transducer with individual elements between about 6-20 wavelengths in length, each of which comprises one or more matching layers.
In yet another embodiment the transducer is a phased array transducer, with elements less than about 1 wavelength in length.
In another embodiment according to the present invention there is provided a device according to the embodiments described wherein at least three transducers are incorporated into the device wherein at least one of each of which comprises:
(a) a single element transducer with multiple matching layers;
(b) a multi-element transducer with individual elements between about 6-20 wavelengths in length; or
(c) a phased array transducer with less than about 1 wavelength in length.
In an embodiment of the present invention the transducer(s) are capable of delivering ultrasound energy at efficiencies over a range of frequencies spanning approximately 70% fractional bandwidth, preferably the transducer(s) is(are) comprised of a xc2xc wavelength front matching layer of a high acoustic impedance material, capable of delivery of acoustic energy at two discrete frequencies. In another embodiment the transducer(s) is(are) comprised of a xc2xd wavelength front matching layer of high acoustic impedance material, capable of delivery of acoustic energy at three discrete frequencies.
In yet another embodiment of a device according to the present invention the transducer material is PZT.
In still a further embodiment, a device according to the invention is constructed of MR-compatible materials chosen from a metal, ceramic or a polymer, preferably the material is a metal and is brass, copper, or stainless steel. More preferably, where the material is a polymer it is Poly(ether ether ketone)PEEK.
In another embodiment the housing of a device according to the present invention further comprises a tube means for infusing a therapeutic agent into a patient.
In yet another embodiment a device according to the present invention further comprises an acoustically transparent catheter.
In another aspect of the present invention there are provided various methods which incorporate a device of the invention. Accordingly, in one embodiment the present invention provides a method for interstitial ultrasound thermal therapy of tissue comprising:
(a) determining the target tissue volume from images;
(b) planning a route of insertion for a device and a heating regime based on the images, the heating regime comprising a sequence of scan rates, transmission frequencies and powers as a function of device angle;
(c) inserting the device into a desired location for the interstitial thermal coagulation of the target tissue volume, the device comprising a multifrequency ultrasound transducer for providing acoustic energy at multiple discrete frequencies with high efficiency, the transducer having at least one matching layer comprising a high acoustic impedance material;
(d) implementing the heating regime by delivering the acoustic energy to the target tissue volume from the device, the acoustic energy having various frequencies selected from the multiple discrete frequencies, and by rotating and translating the device for producing a thermal lesion conformal to the target tissue volume; and
(e) assessing the thermal lesion with imaging.
In yet another embodiment, the present invention provides a method: of delivering high intensity sound pulses for the purposes of activating either sonically or thermally a therapeutic agent to deliver therapy comprising:
(a) determination of the target tissue volume from images;
(b) planning route of insertion and heating regiment based on the images;
(c) insertion of a device according to claim 2 for the interstitial thermal coagulation of tissue into a desired location in tissue;
(d) delivery of heat with continued monitoring of temperature distribution around said device; and
(e) assessment of the efficacy of activation.
Preferably the transducer of these embodiments of methods of the invention is a single element transducer with multiple matching layers.
In another embodiment the transducer is a multi-element transducer with individual elements between about 6-20 wavelengths in length, each of which comprises one or more matching layers.
In yet another embodiment the transducer is a phased array transducer, with elements less than about 1 wavelength in length.
In another embodiment according to the methods of the present invention there is provided a device, according to the embodiments of the device, wherein at least three transducers are incorporated into the device wherein at least one of each of which comprises:
(a) a single element transducer with multiple matching layers;
(b) a multi-element transducer with individual elements between about 6-20 wavelengths in length; or
(c) a phased array transducer with less than about 1 wavelength in length.
In an embodiment of the methods of present invention the transducer(s) used in the methods are capable of delivering ultrasound energy at efficiencies over a range of frequencies spanning approximately 70% fractional bandwidth, preferably the transducer(s) is(are) comprised of a xc2xc wavelength front matching layer of a high acoustic impedance material, capable of delivery of acoustic energy at two discrete frequencies. In other embodiments of the methods the transducer(s) is(are) comprised of a xc2xd wavelength front matching layer of high acoustic impedance material, capable of delivery of acoustic energy at three discrete frequencies.
In yet another embodiment of the methods the transducer material of a device according to the present invention is PZT.
In still a further embodiment of the methods, a device used in the methods is constructed of MR-compatible materials chosen from a metal, ceramic or a polymer, preferably the material is a metal and is brass, copper, or stainless steel. More preferably, where the material is a polymer it is Poly(ether ether ketone)PEEK.
In another embodiment of the methods, the housing of a device according to the present invention, as used in the methods, further comprises a tube means for infusing a therapeutic agent into a patient.
In yet another embodiment, a device used in the methods further comprises an acoustically transparent catheter.
Other features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples while indicating preferred embodiments of the invention are given by way of illustration only. Various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.